Repotrectinib (TPX-0005)

For research use only.

Catalog No.S8583

4 publications

Repotrectinib (TPX-0005) Chemical Structure

CAS No. 1802220-02-5

Repotrectinib (TPX-0005) is a novel ALK/ROS1/TRK inhibitor with the IC50 values of 1.01 nM for WT ALK, 1.26 nM for ALK(G1202R), and 1.08 nM for ALK(L1196M); also a potent SRC inhibitor (IC50 5.3 nM).

Selleck's Repotrectinib (TPX-0005) has been cited by 4 publications

Purity & Quality Control

Choose Selective ALK Inhibitors

Biological Activity

Description Repotrectinib (TPX-0005) is a novel ALK/ROS1/TRK inhibitor with the IC50 values of 1.01 nM for WT ALK, 1.26 nM for ALK(G1202R), and 1.08 nM for ALK(L1196M); also a potent SRC inhibitor (IC50 5.3 nM).
Targets
ROS1 [2]
()		 Trk receptor [2]
()		 WT ALK [1]
(Cell-free assay)		 ALK(L1196M) [1]
(Cell-free assay)		 ALK(G1202R) [1]
(Cell-free assay)
1.01 nM 1.08 nM 1.26 nM
In vitro

TPX-0005 is an orally available and potent ATP-competitive inhibitor against ALK, ROS1, TRKA, TRKB and TRKC recombinant kinases and their corresponding clinical resistant mutants. TPX-0005 demonstrates potent anti-proliferative activity in the range of sub-nanomolar to low nanomolar in a number of human cancer cell lines and engineered stable cell lines expressing the targeted oncogenes or their solvent front mutants, accompanied by inhibition of target phosphorylation and concomitant inactivation of downstream effectors such as ERK, AKT and STAT3[2]. TPX-0005 inhibits H2228 cell migration in a wound healing assay with similar activity to saracatinib. TPX-0005 is able to not only inhibit the wild-type and a broad spectrum of mutant ALKs, but also overcome primary resistance and suppress metastatic features by inhibiting SRC[1].

Assay
Methods Test Index PMID
Western blot
pEGFR / pERK / pAKT / pSTAT3 / pPaxillin / Pyap1 / cleaved caspase-3; 

PubMed: 29433983     


Extracts from the PC9 cell line treated with gefitinib (0.05 μM), TPX-0005 (1 μM), or the double combination for 24 h, were analyzed using the indicated antibodies. Similar results were obtained in three independent experiments.

29433983
Immunofluorescence
pSTAT3(Y705) / STAT3 ; 

PubMed: 29433983     


Representative immunofluorescence images showing total STAT3 and phospho-STAT3 expression and localization (green) in control, gefitinib, TPX-0005 and gefitinib plus TPX-0005 treated PC9 cells. Cell nuclei were stained with DAPI (blue). Right: expression levels and nuclear translocation of phospho-STAT3 were quantified using an ImageStreamX imaging flow cytometer. 

29433983
In vivo In patient derived xenograft tumor models, TPX-0005 treatment results in significant regression of tumors harboring the oncogenic ALK, ROS1 and TRKC fusions. Moreover, in a series of mouse xenograft tumor models, TPX-0005 exhibits marked anti-tumor activity not only in tumors harboring the wildtype oncogenic targets but also in tumors harboring the oncogenes with the solvent front mutations via inhibition of the target phosphorylation[2].

Protocol

Solubility (25°C)

In vitro DMSO 70 mg/mL (196.97 mM)
Ethanol 10 mg/mL (28.13 mM)
Water Insoluble

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 355.37
Formula

C18H18FN5O2
CAS No. 1802220-02-5
Storage powder
in solvent
Synonyms N/A
Smiles CC1CNC(=O)C2=C3N=C(C=CN3N=C2)NC(C4=C(O1)C=CC(=C4)F)C

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
Dosage mg/kg Average weight of animals g Dosing volume per animal ul Number of animals
Step 2: Enter the in vivo formulation ()
% DMSO % % Tween 80 % ddH2O
CalculateReset

Bio Calculators

Molarity Calculator

Molarity Calculator

Calculate the mass, volume or concentration required for a solution. The Selleck molarity calculator is based on the following equation:

Mass (mg) = Concentration (mM) × Volume (mL) × Molecular Weight (g/mol)

  • Mass
    Concentration
    Volume
    Molecular Weight

*When preparing stock solutions, please always use the batch-specific molecular weight of the product found on the via label and SDS / COA (available on product pages).

Dilution Calculator

Dilution Calculator

Calculate the dilution required to prepare a stock solution. The Selleck dilution calculator is based on the following equation:

Concentration (start) x Volume (start) = Concentration (final) x Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2 ( Input Output )

  • C1
    V1
    C2
    V2

* When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and SDS / COA (available online).

The Serial Dilution Calculator Equation

  • Serial Dilutions

  • Computed Result

  • C1=C0/X C1: LOG(C1):
    C2=C1/X C2: LOG(C2):
    C3=C2/X C3: LOG(C3):
    C4=C3/X C4: LOG(C4):
    C5=C4/X C5: LOG(C5):
    C6=C5/X C6: LOG(C6):
    C7=C6/X C7: LOG(C7):
    C8=C7/X C8: LOG(C8):
Molecular Weight Calculator

Molecular Weight Calculator

Enter the chemical formula of a compound to calculate its molar mass and elemental composition:

Total Molecular Weight: g/mol

Tip: Chemical formula is case sensitive. C10H16N2O2 c10h16n2o2

Instructions to calculate molar mass (molecular weight) of a chemical compound:

To calculate molar mass of a chemical compound, please enter its chemical formula and click 'Calculate'.

Definitions of molecular mass, molecular weight, molar mass and molar weight:

Molecular mass (molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.

Molarity Calculator

Mass Concentration Volume Molecular Weight

Clinical Trial Information

NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT03093116 Recruiting Drug: Oral repotrectinib (TPX-0005) Locally Advanced Solid Tumors|Metastatic Solid Tumors Turning Point Therapeutics Inc. February 27 2017 Phase 1|Phase 2

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

Tel: +1-832-582-8158 Ext:3

If you have any other enquiries, please leave a message.

  • * Indicates a Required Field
selleck catalog

ALK Signaling Pathway Map

Related ALK Products

  • Lorlatinib (PF-6463922) New

    Lorlatinib (PF-6463922) is a potent, dual ALK/ROS1 inhibitor with Ki of <0.02 nM, <0.07 nM, and 0.7 nM for ROS1, ALK (WT), and ALK (L1196M), respectively. PF-06463922 induces apoptosis. Phase 1.

  • Erlotinib (OSI-774) New

    Erlotinib (OSI-774, CP358774, NSC 718781, Tarceva) is an EGFR inhibitor with IC50 of 2 nM, >1000-fold more sensitive for EGFR than human c-Src or v-Abl. Erlotinib induces autophagy.

  • Bemcentinib (R428) New

    Bemcentinib (R428, BGB324) is an inhibitor of Axl with IC50 of 14 nM, >100-fold selective for Axl versus Abl. Selectivty for Axl is also greater than Mer and Tyro3 (50-to-100- fold more selective) and InsR, EGFR, HER2, and PDGFRβ (100- fold more selective).

  • TAE684 (NVP-TAE684)

    TAE684 (NVP-TAE684) is a potent and selective ALK inhibitor with IC50 of 3 nM in a cell-free assay, 100-fold more sensitive for ALK than InsR. TAE684 (NVP-TAE684) induces cell cycle arrest and apoptosis.

  • GSK1838705A

    GSK1838705A is a potent IGF-1R inhibitor with IC50 of 2.0 nM, modestly potent to IR and ALK with IC50 of 1.6 nM and 0.5 nM, respectively, and little activity to other protein kinases.

    Features:A small-molecule kinase inhibitor of IGF-1R and the insulin receptor.

  • Alectinib (CH5424802)

    Alectinib (CH5424802, AF-802, RG-7853) is a potent ALK inhibitor with IC50 of 1.9 nM in cell-free assays, sensitive to L1196M mutation and higher selectivity for ALK than PF-02341066, NVP-TAE684 and PHA-E429.

  • ASP3026

    ASP3026 is a novel and selective inhibitor for ALK with IC50 of 3.5 nM. Phase 1.

  • AZD3463

    AZD3463 is a novel orally bioavailable ALK inhibitor with Ki of 0.75 nM, which also inhibits IGF1R with equivalent potency. AZD3463 suppresses cell viability by inducing both cell apoptosis and autophagy.

  • Ceritinib (LDK378)

    Ceritinib (LDK378) is potent inhibitor against ALK with IC50 of 0.2 nM in cell-free assays. Ceritinib (LDK378) also inhibits IGF-1R, InsR, STK22D and FLT3 with IC50 of 8 nM, 7 nM, 23 nM and 60 nM, respectively. Phase 3.

    Features:Does not cross react with c-Met, and has an improved in vivo glucose homeostasis profile relative to TAE684. May be active in Crizotinib-relapsed tumors.

  • Gefitinib (ZD1839)

    Gefitinib (ZD-1839, Iressa) is an EGFR inhibitor for Tyr1173, Tyr992, Tyr1173 and Tyr992 in the NR6wtEGFR and NR6W cells with IC50 of 37 nM, 37nM, 26 nM and 57 nM, respectively. Gefitinib promotes autophagy and apoptosis of lung cancer cells via blockade of the PI3K/AKT/mTOR pathway.

    Features:A potent EGFR tyrosine kinase inhibitor.

Tags: buy Repotrectinib (TPX-0005) | Repotrectinib (TPX-0005) supplier | purchase Repotrectinib (TPX-0005) | Repotrectinib (TPX-0005) cost | Repotrectinib (TPX-0005) manufacturer | order Repotrectinib (TPX-0005) | Repotrectinib (TPX-0005) distributor
×
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID